The Center for HIV/AIDS Vaccine Immunology (CHAVI) will be an extramural HIV/AIDS vaccine center consortium whose overall mission is to address key immunological roadblocks to HIV-1 vaccine development and to design, develop, and test novel immunogens and adjuvants. The CHAVI consortium will be comprised of the Principal Investigator (B. Haynes, Duke), Senior Leadership Group members (N. Letvin, Harvard;J. Sodroski, Harvard;G. Shaw, UAB;A. McMichael, Oxford), and Core Leaders (S. Harrison, Harvard;R. Dolin, Harvard;D.Goldstein, Duke;and M. Cohen, UNC). Overall goals of the CHAVI consortium will be: 1) To elucidate early viral and immunological events and host genetic factors associated with HIV-1 transmission, establishment of infection, and (partial) containment of virus replication;2) To determine correlates of SIV immune protection in primates;3) To design, develop, and test novel immunogens and adjuvants that elicit persistent mucosal and/or systemic immune responses to HIV-1 and SIV in humans and primates;and 4) To evaluate HIV-1 vaccine candidates in early phase clinical trials. The centerpiece of the CHAVI research agenda is the principal investigator's R01 project, which has four aims: 1) characterization of transmitted HIV-1;2) ontogeny of cellular immune responses in acute and early HIV-1 infection;3) ontogeny of humoral immune responses in acute and early HIV-1 infection;and 4) host genetic factors influencing HIV-1 infection and early progression. These aims, in turn, are closely linked to senior leadership group research projects: Neutralization properties of transmitted HIV-1 (Shaw); Viral, immunological, and host genetic factors in HIV-1 exposed-uninfected individuals (McMichael); Correlates of immune protection in SIV vaccinated macaques (Letvin);and Structure of transmitted HIV-1 envelope trimers (Sodroski). A major strength of the CHAVI is the breadth and depth of vaccine-related research that it will undertake, the opportunities for unique synergies among its participants, and the demonstrated abilities of the principal investigator in leading a large basic and clinical research enterprise. The CHAVI Consortium will be an integral component of the Global HIV-1 Vaccine Enterprise. It will address critical gaps in scientific knowledge and will contribute in a direct and meaningful fashion to the successful development of an efficacious and globally applicable HIV-1 vaccine.